The conventional evaluation of cardiac muscle cells was carried out, for example, in such a manner that cardiac muscle cells were isolated and extracted from a cardiac organ of a laboratory animal, they were cultured on a laboratory dish or the like to prepare primary cultured cells, and the primary cultured cells were used to evaluate the cardiac muscle cells. During the primary culture, cells grow horizontally in a monolayer state (in a sheet shape) in a certain period and the cardiac muscle cells come to beat (contract and relax) in synchronization. However, such primary cultured cells are not human cells and thus are not suitable for use in evaluation of cardiotoxicity or the like on human cardiac muscle cells because of the difference of species.
In recent years, with progress of technologies to culture stem cells such as iPS cells or ES cells, it became feasible to artificially create aggregated cells being a three-dimensional aggregate of cells and evaluation of the aggregated cells (e.g., evaluation of change of the aggregated cells upon administration of a drug) has been becoming important. To conduct evaluation of drug efficacy using the cardiac muscle cells prepared from human iPS cells or human ES cells as a specimen is extremely important in evaluation of drug efficacy and safety because it can be done by use of cells of human origin. A cardiac muscle tissue, which is a three-dimensional aggregate of cardiac muscle cells created from human iPS cells or human ES cells, is a tissue in which not only the cardiac muscle cells but also fibroblast cells and others for holding the peripheries of the cells are cultured in mixture, and thus it is feasible to perform the evaluation under a condition similar to a human heart.
Here, Non Patent Document 1 suggests the evaluation method for sheet-shaped cells being a two-dimensional aggregate of cells. Since the sheet-shaped cardiac muscle is obtained by sampling the cardiac muscle cells nearly 100% and culturing them, the evaluation of the sheet-shaped cardiac muscle is evaluation in a state different from the real heart. Further, since the sheet-shaped cells adhere individually to a base plate such as the bottom of a laboratory dish, the adhesion inhibits change in motion to be caused by drug effect and thus such cells do not allow accurate evaluation of motion.
In contrast to it, aggregated cells are less affected by the inhibition effect as to motion of cells located in regions away from the base plate, though motion of cells near the base plate is inhibited by adhesion to the base plate. Therefore, the aggregated cells allow more accurate evaluation of motion than the sheet-shaped cells, and are more likely to physiologically reflect the change in motion to be caused by drug effect, the aggregated cells are thus in a favorable state for evaluation of cardiotoxicity or the like in drug discovery.